This chapter indicates that schizotypal personality disorder (SPD) is a disturbance that may be genetically related to schizophrenia. It argues that SPD research is of key importance in overcoming methodological weaknesses of schizophrenia research. The chapter outlines some of conceptual and theoretical issues in directing research along productive lines. These issues are grouped under the following headings: diagnostic issues, phenomenological and assessment issues, methodological issues, mechanisms and etiology, and clinical issues. SPD is viewed as an Axis II disorder alongside other personality disorders. Clinical studies of SPD recruit subjects from a hospital sample; or alternatively, they are recruited from the community and have not previously been hospitalized. The control groups in clinical research may include borderline personality disorder, which has been closely associated with SPD; or an Axis II disorder that is unrelated to schizophrenia spectrum disorders, such as self-defeating personality disorder.