Functional MRI is a new and exciting method for studying the human brain as it functions in its living, natural state. As the field grows and the methodology improves, so do the many computational and statistical problems that accompany the storage, processing, analysis, and interpretation of the data. In this chapter we have briefly summarized some of the complexities and limitations of the method as well as describing some of the approaches available for addressing these complexities and limitations. The field of fMRI will, no doubt, continue to broaden and expand. As it does so, the continued integration of scientists and researcher from many disciplines will be necessary for fMRI to reach its full potential and to help to uncover one of the greatest mysteries of humankind.