The main issue with this question, as with all interview questions, is to maintain a positive stance - even if the reason for leaving that last position was due to job performance, poor fit, career change situations, money, politics, boredom, personality conflict, or any of the usual reasons. Even when the job move is intended to add a credential or challenge, an acceptable reason for changing jobs, it's difficult to make yourself look good when you're suggesting that the last position was problematic in any way at all.
A great way, then, to remember to keep this issue as positive as possible, is a new commandment: "Thou shalt never speak ill of thy former employer!" Many clients have interpreted this to mean that an interviewee shouldn't trash that former job because prospective employers might think you'd do that with them, too. That could be true, but the real problem in presenting a negative situation is creating the impression that the applicant is some kind of malcontent. Negatives always have some kind of unwanted effect on interviewers, even if the story is perfectly understandable, even if the interviewer sympathizes with the tragic circumstances.
I strongly suggest that the answer to this question should be prepared well in advance of any self-marketing, especially interviewing. It's also advisable to make sure that you're keeping the prospective employer's interests ahead of your own in the interview. Saying "I left to seek better opportunities" - which could sound self-serving - would be stated better as "I'm looking for a situation which will more completely utilize my skills and experience in...," which offers the opportunity to present those skills and experiences, rather than a defensive, over-explained reaction. With these kinds of questions, it's always best to keep it short and simple. When in doubt, try to turn everything around into demonstrating your knowledge and skill bases.
Of course, the above presents a generalized stance, and ignores some of the more individual and personal issues in dealing with this difficult interview question. We'll take some of those up in future columns, and on the Interviewing bulletin board.
This question is among the most basic in interviewing. It's also one of the trickiest, as an interviewee can be eliminated from consideration with a poorly conceived response.