Research to understand the genetic basis of disease, particularly complex disease, regularly involves single nucleotide polymorphism (SNP) genotyping. The use of genome-wide SNP genotyping arrays has become increasingly more commonplace for gene discovery. However, smaller-scale genotyping platforms capable of efficiently genotyping tens to hundreds of SNPs are still crucial for many aspects of this work, including replication of associations. The Agena Bioscience MassARRAY System is one such platform. Here, we provide a guide to using the MassARRAY System, from assay design, through mass spectrometry, to generation of genotype data.