REJECTION! The word itself sounds menacing but it's a normal part of academic life. Very few of us (maybe none?) have never had a paper rejected from a scientific journal. We're all members, willing or not, of Rejection Club.
I'll start by confessing my "dirty" secret. In the last year, I have received EIGHT rejections from scientific journals! I hope that makes some of you feel a little better. Of course, it' not fair to say that they were eight separate rejections. Six were rejections from very high impact journals that didn't even send the papers out for review (four were actually the same paper). Experiencing rejection on such a scale has taught me some very important lessons.
The first rule of Rejection Club is...it happens to everyone! You know that professor whose work is constantly published in Nature or Science? They've been rejected more times than you will be during your entire MSc or PhD (possibly your entire career). Moreover, all of the graduate students I talk to have had papers rejected from journals with both high and low impact factors. If you're determined to be an academic, you better grow a thick skin and get used to the idea!
The second rule of Rejection Club is...don't take it personally. The first question I asked when my first paper was rejected in 2008 was "Does this mean I am a terrible scientist?" The answer to this question is usually no but my automatic response was to feel upset and embarrassed. Of course, I have experienced several more rejections since and realized that an emotional response is usually unwarranted (although it hasn't stopped me from having one every once in awhile!). Once I started receiving invitations to review manuscripts, I realized that the goals of MOST reviewers are to i) honestly help improve the paper and ii) simply guide the journal in making a publication decision. Although I have seen some manuscripts that needed considerable revision, I have never judged the authors (after all, I've been in their shoes!!!).
The third rule of Rejection Club is...seriously consider all reviewer comments. You might be saying "DUH!" But the fact of the matter is that some reviewer comments can sound utterly inappropriate. I have definitely asked "was that reviewer high when they read my paper?" However, comments that don't make sense or seem unrelated might point to a more serious problem with your paper (e.g., unclear explanation and writing). You should try to clarify any areas of confusion in new versions of the manuscript. After all, you might get the same reviewer(s) on the second round.
The fourth rule of Rejection Club is...balance impact and quick publication. I have only recently come to terms with the fact that the ultimate goal during my PhD should be to publish many papers, quickly (again, DUH, but I was stuck on trying to get that one, life altering Nature paper). It's a matter of fact that journals like Nature and Science reject a very large portion of the submissions they receive without sending them for external review (trust me, I have experience). After such a rejection you're left with very little to work with because they provide very little feedback. After submitting to two other high impact journals (and getting advice from various advisers), I realized that I had nothing to show for months of work, not even constructive reviewer comments. After seeking the advice of several advisers, I realized (rather, they helped me realize) that if I had submitted to a mid-range journal, my paper would be published by now. Ultimately, the success of your PhD is partially measured in the number of good/acceptable (rather than amazing) papers you publish.
The fifth rule of Rejection Club is...rejection makes your paper better. It's confirmed, papers that are rejected and re-submitted are cited more often than papers that aren't (http://www.sciencemag.org/content/338/6110/1065)! Rejection might actually increase the awesomeness of your paper. It's really easy to become myopic when working on a project or paper for a long time. Comments from a diverse array of reviewers and editors will improve the quality and ultimately the reception of your paper by the scientific community. Rejection, although frustrating, can be a good thing. So keep on submittin'.
I am absolutely certain there are more rules of Rejection Club. Post them in the comments!