The 2012 Congress of the Society for Melanoma Research was attended by researchers with widespread expertise in basic, translational, and clinical research. Exciting research has led to the discovery of therapies to target mutations found in melanoma; however, it is clear that much still needs to be learned about how to use these therapies and the role of the microenvironment in therapy resistance and melanoma progression. This summary highlights recent discoveries in genetics and epigenetics, biology, immunotherapy, and targeted therapies for melanoma discussed at this year's meeting.