Selective serotonin reuptake inhibitors (SSRIs) remain first-line drugs for treating late-life depression (Alexopoulos et al. 2001; Pinquart et al. 2006) because of their efficacy for both depressive and anxiety syndromes, their ease of use, and their safety and good tolerability. As with most drugs, few clinical trials of SSRIs have been conducted under "real-life" geriatric situations (e.g., in long-term care facilities) or in very old patients. However, as of June 2007, more than 30 randomized, controlled trials of SSRIs involving more than 5,000 geriatric patients with depression had been published (Table 26–2). Those age 70 and older who have experienced major depression are at high risk for relapse. Maintenance SSRI therapy has been shown to be an effective treatment (Gorwood et al. 2007; Reynolds et al. 2006). Several controlled and open studies also have been conducted in special populations (Solai et al. 2001); reviews of many of these trials concluded that SSRIs are efficacious, safe, and well tolerated in older patients, including those with mild cognitive impairment (Devanand et al. 2003), dementia (Katona et al. 1998; Lyketsos et al. 2003; Nyth and Gottfries 1990; Nyth et al. 1992; Olafsson et al. 1992; Petracca et al. 2001; Taragano et al. 1997), minor depression (Rocca et al. 2005), schizophrenia (Kasckow et al. 2001), cardiovascular disease (Glassman et al. 2002; Serebruany et al. 2003), cerebrovascular disease (Y. Chen et al. 2007; Rasmussen et al. 2003; Robinson et al. 2000), or other medical conditions (Arranz and Ros 1997; Evans et al. 1997; Goodnick and Hernandez 2000; Karp et al. 2005; Lotrich et al. 2007; Trappler and Cohen 1998).