Laboratory testing is essential for diagnosing bleeding disorders. The tests and panels that laboratories currently use for bleeding disorder evaluation are not standardized, although most offer coagulation screening tests in bleeding disorder panels. Some tests for bleeding disorders, including von Willebrand factor multimer assays and tests for rarer disorders, are not widely available. Accordingly, clinicians and laboratories need tailored strategies for evaluating common and rare bleeding disorders. Coagulation screening tests have high specificity, however, false positives and false negatives do occur among subjects evaluated for bleeding disorders and more specific tests (e.g., factor assays) are required to further assess abnormalities. Tests for defects in primary hemostasis have similar high specificity but much greater sensitivity for common bleeding disorders than coagulation screening tests. Nonetheless, extensive testing fails to establish a diagnosis in a significant number of individuals considered to have significant bleeding problems. Rare bleeding disorder investigations are important to diagnose some conditions, particularly those with delayed-onset bleeding, such as factor XIII deficiency, α2 antiplasmin deficiency, plasminogen activator inhibitor-1 deficiency, and Quebec platelet disorder. These issues need careful consideration when assessing patients for congenital and acquired bleeding problems.