Continuing research on tardive dyskinesia has considerably broadened the classic hypothesis of dopamine-receptor supersensitivity, proposed more than 20 years ago (Klawans, 1973). Roles for other neurotransmitter systems (GABA and norepinephrine) have been postulated (Tamminga, Crayton, & Chase, 1979; Wagner et al., 1982; Fibiger & Lloyd, 1984; Gunne, Haggstrom, & Sjoquist, 1984; Jeste, Doongaji, & Linnoila, 1984; Stahl et al., 1985; Kaufman et al., 1986; Thaker et al., 1987; Andersson et al., 1989; Thaker, Nguyen, & Tamminga, 1989), and there is a newer hypothesis suggesting that cellular damage mediated by free radicals underlies tardive dyskinesia (Lohr et al., 1988, 1990; Cadet & Lohr, 1989). Demographic and psychiatric variables, such as gender, age, and concomitant affective disorder, have also been identified as risk factors (Smith & Baldessarini, 1980; Jeste & Wyatt, 1982; Kane & Smith, 1982; Richardson et al., 1985; Kane et al., 1986; Weiner & Lang, 1989). Increasingly, these disparate variables support the concept that tardive dyskinesia, like most brain dysfunctions, may involve multiple abnormalities and that vulnerability to it may be multifactorial. In this chapter we summarize our findings concerning risk factors for tardive dyskinesia that suggest that amino acid metabolism – particularly that of the large neutral amino acid phenylalanine (Phe) – may play a role in vulnerability to tardive dyskinesia.