Stable isotope labeling by amino acids (SILAC) metabolically encodes cell populations for protein quantification by mass spectrometry. SILAC was introduced in 2002 and the field of mass spectrometry based proteomics has changed dramatically over the last decade. Increased sensitivity and speed of mass spectrometry instruments coupled with significantly improved mass resolution and precision have led to much higher rates of peptide identification and deeper coverage of proteomic samples. Several proteomics approaches are now available for quantifying proteins and their post-translational modifications, each with their strengths and weaknesses. The simplicity and robustness of SILAC have led to its widespread adoption and new applications have emerged that play to its particular strengths as a metabolic labeling approach.