This chapter discusses the components of the behavioral phenotype in velo-cardio-facial syndrome (VCFS), namely, the high rates of behavioral and psychiatric disorder seen in VCFS children and adults. It summarizes the principal studies of the psychiatric phenotype in VCFS individuals. The most reliable criteria to determine whether the association between VCFS and schizophrenia is valid should involve: increased frequency of schizophrenia in VCFS individuals, increased frequency of VCFS in people with schizophrenia and susceptibility locus for schizophrenia should map to 22q11.2. A major goal of psychiatric and especially schizophrenia research over the past three decades has been the identification of precursor symptoms and areas of dysfunction in children and adolescents which precede the later development of major psychiatric disorder in adults. Difficult behaviors seen in children with VCFS can be approached using behavioral modification techniques including the use of token economies and reward schemes.