The advent of genome-scale molecular instrumentation has led to an explosion of biomedically relevant data, with nonstop exponential improvements in performance likely to continue for decades. We are truly at an infection point in the history of life and medicine. However, this deluge presents a signifcant challenge: making sense of genome scale data is increasingly the fundamental task in molecular biology. In this brief tutorial, we will explore the different sorts of explanations that play a role in understanding life, the sources of knowledge about genes and their effects, and the process of integrating knowledge and data about multiple genetic differences into a coherent story about mechanism.