Magnetic resonance imaging (MRI) allows the assessment of functional changes consequent to drug administration. Two main approaches have been used: changes in functional MRI signal following drug injection compared to the signal prior to injection and changes in task-related brain networks on drug compared to placebo. Here we describe the additional constraints drug studies place on subject selection, study designs and additional technical requirements. Critical issues in the design of statistical analysis routines are described, including the incorporation of peripheral markers of drug action, such as heart and respiration rate, as well as pharmacokinetic data. Finally, we address methods to minimise the potential influence of non-specific drug effects and side effects on the MRI signal allowing interpretation more closely aligned to the precise research questions.