Very few people enjoy job interviews. They can be particularly nerve-wracking if you're up for the job of your dreams or have been unemployed for a long while. The stress and nerves are bad enough without your interviewer throwing you a curve-ball of a question you haven't got a clue how to field. You can limit the chances of this happening by preparing well for your meeting. If an ambiguously worded question raises its head nonetheless, be honest and ask the person interviewing you what he means.
Research the company before you attend your interview. Also, make sure you're fully aware of what the role you've applied for involves. A question may seem ambiguous to a candidate who hasn't prepared. If you've read up on the business and nature of the job, you'll be better equipped to field any awkward questions that may come your way. Go further than just perusing the company's website: Run an Internet search and make sure you're reading from a range of reliable sources.
Have answers prepared for common interview questions. Sometimes, a generic question along the lines of "Tell me about a time you worked well under pressure" can throw you more than being asked about a complicated theory or process. Run through some answers to questions like these before you attend your interview. You can find lists of commonly asked interview questions online.
Listen intently to the questions your interviewer asks you; take a moment to digest them if they seem unclear initially.
Ask the interviewer to repeat her question if you have trouble making sense of it. If you still don't get it, ask her to explain the question in more detail. It's better to be honest and ask for clarity than cobbling together a rambling answer.
Answer the question as best you can after your interviewer has explained it to you. If you're still unsure about the nature and intent of the question, start your response with: "If my interpretation of the question is correct, I would say...."