Osteoarthritis is a heterogeneous disease characterized by variable clinical features, biochemical/genetic characteristics, and responses to treatments. To optimize palliative effects of current treatments and develop efficacious disease-modifying interventions, treatments may need to be tailored to the individual or a subset of osteoarthritic joints. The purpose of this review is to explore the current literature on the clinical and physiological variability in osteoarthritis and potential for stratifying patients. Several stratifications have been reported, including mechanism of onset, stage of disease progression, involved joints, inflammatory levels, and effusion. Most of these methods revealed two to three unique subsets of osteoarthritis. Osteoarthritic joints may be stratified by an array of variables, some transient and others consistent throughout the disease process. Future research needs to continue to explore stratification techniques since these may be the key to optimizing palliative interventions and developing disease-modifying interventions for subsets within this heterogeneous disease.