Abstract Objectives Given the conflicting definitions of “generalized osteoarthritis” (GOA) in the literature, we performed a systematic review of GOA definitions, risk factors, and outcomes. Methods We searched the MEDLINE literature with the terms osteoarthritis, generalized, polyarticular, multiple joint, and multi-joint to obtain articles related to GOA, following evidence-based guidelines. Titles and abstracts of 948 articles were reviewed, with full-text review of 108. Data were extracted based on pre-specified criteria for 74 articles plus 24 identified through bibliographic review ( n = 98). Results Twenty-four large cohorts ( n ~ 30,000) were represented along with numerous clinical series ( n ~ 9000), across 22 countries and 60 years (1952–2012). No less than 15 definitions of GOA were given in 30 studies with a stated GOA definition; at least 6 groups used a summed score of joints or radiographic grades. Prevalence estimates based on these GOA definitions were 1–80%, although most were 5–25%. Increased risk and progression of GOA was associated with age, female sex, and genetic/familial factors. Associations with increased body mass index or bone mineral density were not consistent. A study estimated the heritability of GOA at 42%. Collagen biomarker levels increased with the number of involved joints. Increased OA burden was associated with increased mortality and disability, poorer health, and function. Conclusion While there remains no standard definition of GOA, this term is commonly used. The impact on health may be greater when OA is in more than one joint. A descriptive term, such as multi-joint or polyarticular OA, designating OA of multiple joints or joint groups is recommended.