It has been observed that 'No aspect of human behavioral genetics has caused more confusion and generated more obscurantism than the analysis and interpretation of various types of non-additivity and non-independence of gene and environmental action and interaction' (Eaves LJ et al 1977 Br J Math Stat Psychol 30:1-42). On the other hand, a bulk of newly published studies appear to speak in favour of common and frequent interplay - and possibly interaction - between identified genetic polymorphisms and specified environmental variables in shaping behavior and behavioral disorders. Considerable interest has arisen from the introduction of putative functional 'endophenotypes' which would represent a more proximate biological link to genes, as well as an obligatory intermediate of behavior. While explicit criteria to identify valid endophenotypes have been offered, a number of new 'alternative phenotypes' are now being proposed as possible 'endophenotypes' for behavioral and psychiatric genetics research, sometimes with less than optimal stringency. Nonetheless, we suggest that some endophenotypes can be helpful in investigating several instances of gene-environment interactions and be employed as additional tools to reduce the risk for spurious results in this controversial area.