In this chapter, the multiple use-case scenarios in which functional MRI can be used for cognitive neuroscience are reviewed: cognitive/psychology experiments, biomarking studies (observational, experimental, and genetic), and intervention studies (treatments and pharmacological effects). In each case, a detailed and up-to-date account of designs and experimental methodologies is provided. For this third edition, the chapter has been completely rewritten, and the most recent methodological developments and controversies are discussed throughout, setting fMRI in context, and providing the reader a better understanding of how and when fMRI can be leveraged to answer questions about cognition.