The systemic vasculitides, if left untreated, often lead to major organ damage and death. When a patient presents with features that may be consistent with vasculitis, especially with pulmonary and renal findings, it is important to make a specific diagnosis as quickly as possible so that specific therapy can be started. Diagnosis is dependent on familiarity with the myriad of typical and unusual clinical features of the various vasculitides together with performance of supportive tests including serologies, angiograms, and biopsies. When evaluating a potential case of vasculitis, clinicians must comprehensively search for other more common, non-vasculitic diseases. The diagnosis may be even more difficult in patients with established diagnoses of vasculitis on immunosuppressive treatment who develop new clinical findings. Rapid initiation of immunosuppressive therapy for critically ill patients with vasculitis is crucial and may be life-saving.