This systematic review describes human molecular imaging studies which have investigated alterations in extracellular DA levels during performance of behavioral tasks. Whilst heterogeneity in experimental methods limits meta-analysis, we describe the advantages and limitations of different methodological approaches. Interpretation of experimental results may be limited by regional cerebral blood flow (rCBF) changes, head movement and choice of control conditions. We revisit our original study of striatal DA release during video-game playing [Koepp, M.J., Gunn, R.N., Lawrence, A.D., Cunningham, V.J., Dagher, A., Jones, T., Brooks, D.J., Bench, C.J., Grasby, P.M., 1998. Evidence for striatal dopamine release during a video game. Nature 393, 266-268] to illustrate the potentially confounding influences of head movement and alterations in rCBF. Changes in [(11)C]raclopride binding may be detected in extrastriatal as well as striatal brain regions-however we review evidence which suggests that extrastriatal changes may not be clearly interpreted in terms of DA release. Whilst several investigations have detected increases in striatal extracellular DA concentrations during task components such as motor learning and execution, reward-related processes, stress and cognitive performance, the presence of potentially biasing factors should be carefully considered (and, where possible, accounted for) when designing and interpreting future studies.