Lethargy and weakness are common presenting signs in first-opinion practice but can be difficult to distinguish for both the owner and clinician. They may be primary signs but are more commonly secondary to another disease process. Many conditions can result in lethargy and/or weakness, and in order to determine the exact cause of the signs, a full history should be obtained and clinical examination and diagnostic work-up performed. This chapter looks at history, physical examination, differential diagnosis, diagnostic tests and endocrine disorders causing lethargy and weakness.