Rheumatologic disorders are in many ways heterogeneous diseases.They have an array of clinical manifestations, involve multiple organs, produce unpredictable flares, and have widely varying clinical outcomes. Diagnosing rheumatologic diseases and predicting outcomes in a reliable way could lead to new therapeutic strategies and optimization of care. This article reviews the current literature on biological and clinical markers related to diagnosing disease, assessing for disease activity, and predicting outcomes for selected rheumatologic conditions.