The shoulder is the site of multiple injuries and inflammatory conditions that lend themselves to diagnostic and therapeutic injection. Joint injection should be considered after other therapeutic interventions such as nonsteroidal anti-inflammatory drugs, physical therapy, and activity-modification have been tried. Indications for glenohumeral joint injection include osteoarthritis, adhesive capsulitis, and rheumatoid arthritis. For the acromioclavicular joint, injection may be used for diagnosis and treatment of osteoarthritis and distal clavicular osteolysis. Subacromial injections are useful for a range of conditions including adhesive capsulitis, subdeltoid bursitis, impingement syndrome, and rotator cuff tendinosis. Scapulothoracic injections are reserved for inflammation of the involved bursa. Persistent pain related to inflammatory conditions of the long head of the biceps responds well to injection in the region. The proper technique, choice and quantity of pharmaceuticals, and appropriate follow-up are essential for effective outcomes.