This video explains how to answer one of the five toughest job interview questions, this one being "what are your greatest weaknesses?" In it John Heaney of "The Job Shopper" explains that the most important thing about this question is to realize that answering in a way that really paints a negative picture of yourself will negatively impact your potential employment.
The first step is to acknowledge that as human beings we all have weaknesses and to realize that the interviewer is aware of this and is trying to gauge how honest you are with your own personal assessment at acknowledging your own shortcomings. In order to answer this question you have to think about yourself in order to come up with a relevant weakness and how you use your strengths to overcome it.
Avoid responses such as you work too hard, or you have to insure that everything you do is perfect. They are looking for an answer that demonstrates that you are honest, truthful, and insightful.
For example if you have trouble staying organized you can explain how you use several tools to track deadlines, projects, and calls as well as delegating specific tasks to your assistant in order to make sure that everything is kept up to date.