INTRODUCTION: Hypothyroidism is six times more common in women, affecting up to 40 in 10,000 each year (compared with 6/10,000 men). METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for clinical (overt) hypothyroidism? What are the effects of treatments for subclinical hypothyroidism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found nine studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: levothyroxine, and levothyroxine plus liothyronine.