Genetic polymorphisms in drug metabolizing enzymes are important contributors to inter-individual variability in drug response and can lead to adverse reactions or therapeutic failure. Understanding polymorphisms in humans responsible for such differences could lead to development of safer medications, specific to an individual’s genetic traits. Despite the intense interest to understand how amino acid variations impact enzyme activity, the structural and functional basis of single nucleotide polymorphisms is limited. The objective of this symposium is to elucidate the impact of polymorphisms on enzyme expression, function, as well as drug binding and activation using structural, biophysical, functional, and computational genomic approaches.