The RYR1 gene encodes the ryanodine receptor isoform 1 (RYR1), a homotetrameric calcium channel found on the terminal cisternae of the sarcoplasmic reticulum (SR) of skeletal muscle, cardiac muscle, smooth muscle cells, and the endoplasmic reticulums of B-lymphocytes and cerebellar Purkinjie cells. RYR1 plays a critical role in calcium release and muscle contraction in skeletal muscle. Many RYR1 variants are implicated in neuromuscular diseases of varying severity and dozens of genetic variants in RYR1 influence patient risk for developing drug-induced myopathies such as malignant hyperthermia (MH) [1, 2]. MH is a potentially lethal condition triggered by potent inhalational anesthetics and depolarizing muscle relaxants. The incidence of MH is rare; estimates of the incidence of MH range from 1 of 10,000 to 1 of 250,000 anesthesias. However, the genetic prevalence of MH susceptibility (MHS) has been estimated to be as high as 1 out of 400 individuals [2]. The American College of Medical Genetics (ACMG) 2013 report on recommendations for clinical exome and whole genome sequencing analyses includes RYR1 in its list of genes to report in incidental findings [3]. This review will focus on RYR1 in skeletal muscle because it is the primary locus for MHS and will also explore the potential impact of genetic variation in RYR1 on other drug-induced myopathies accompanying the use of HMG Co-A reductase inhibitors (statins). An interactive version of this review can be accessed at (https://www.pharmgkb.org/gene/PA34896).