Protein N-methylation has recently emerged as a major mechanism involved in regulating gene transcription and epigenetic inheritance. Transcriptional coactivators and corepressors have both been shown to associate with protein N-methyltransferases. These enzymes methylate arginine or lysine residues within histones as well as other proteins, such as transcription factors. Here, we discuss the recent advances in our understanding of protein methylation and its involvement in gene expression. Protocols are presented for studying transcriptionally relevant protein methylation.