Great question. The simple answer is honesty. But to be more specific, polished honesty. As someone who has done all levels of recruiting and contracting, honesty takes you a long way.

A few tips: regardless of why there was a gap (let go from a job, bad situation, went back to school etc.) remain positive. We love to see what you learned or were able to take away from your experience.
Also, don't exclude failures from the conversation. Don't make them the focus of an interview, but I loved to meet people who acknowledged times when they had failed, showed me how they learned from it, and most importantly how they overcame and moved forward. Failure is a great learning tool if you choose to see it that way.

Don't let a gap in your resume hinder you from going after what you really want. The worst you can hear is feedback on why you might not be a great fit. Take it constructively and prepare for something that will be the right fit to propel your career to the next level.

Good luck!