This chapter appraises prototypical genomic variation with impact on gene expression, and complementary studies of gene and environmental effects on brain development and synaptic plasticity in the mouse model. Special emphasis is given to molecular mechanisms of neurodevelopmental genetics. Relevant conceptual and methodological issues pertinent to the dissection of the psychopharmacogenetic-neurodevelopmental interface are also considered. Many genes that influence complex traits and psychopharmacological drug responses are likely to be distributed continuously. Such genes are referred to as quantitative trait loci. Connecting drug response with relevant functional DNA variants in the brain and with differences in gene expression in brain regions represents the ultimate goal for pharmacogenetic research. The serotonergic gene pathways is a rewarding area of investigation because of numerous and essential functions of the central serotonin (5-HT) system, the wealth of drug targets within this system, and the range of serotonergic compounds available in the clinical setting.