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This essay reviews Vygotsky’s work on defectology. First, his defectological writing is situated within three contexts: his formative perspective developed within Jewish culture, his rejection of a Christian perspective of charity toward people of difference, and in relation to Marxist principles. The review then outlines his perspective on the “defect,” including his definition of “defect,” his view of the generative potential of overcoming the obstacles of biological difference, and his consideration of the secondary defect of low self-worth that follows from being treated as different and defective. Finally, the review considers his defectological writing as part of his broader effort to formulate a theory of situated, mediated human development.