Epidemiological and clinical evidence suggests estrogen plays a role in the development and severity of schizophrenia, and a growing body of literature indicates estrogen therapy is a feasible treatment option. Current pharmacological treatments for schizophrenia primarily address the positive symptoms and fail to adequately address the cognitive deficits; thus, novel treatments require exploration. The sex steroid hormone 17β-estradiol has been extensively studied as a treatment for schizophrenia, and selective estrogen receptor modulators (SERMs) have been more recently investigated as other potential candidates. This chapter aims to critically analyse the current evidence for the clinical applicability of 17β-estradiol and the SERM raloxifene for the treatment of schizophrenia, with particular emphasis on treating cognitive symptoms.