This chapter examines the role of investigations in diagnosis, assessing disease activity, and monitoring treatment in rheumatic disease. It reviews the relevance of haematology and biochemistry tests in clinical context, including differential diagnosis of anaemia and cytopenia which may reflect the disease process, co-morbidity, or adverse drug effects. Bone biochemistry and markers are also described. Autoantibodies are important in diagnosis and prognosis in rheumatology. Interpretation of rheumatoid factor, anti-cyclic citrullinated peptide (CCP) antibodies, antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), extractable nuclear antigens (ENA), antiphospholipid antibodies, and also HLA-B27 is discussed. Arthrocentesis is a technique specific to rheumatology, and neurophysiology is useful in distinguishing neurological versus inflammatory muscle disease, in addition to nerve entrapment syndromes and neuropathies. The chapter also introduces the use of diagnostic imaging and early identification of inflammatory arthritis, including X-ray, ultrasound, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), nuclear medicine bone scintigraphy, and dual-energy X-ray absorptiometry (DXA).