Aspects of neuropsychological assessment are used in a wide range of clinical and research settings. Over the past half century, in conjunction with the recognition that American Sign Language (ASL) is indeed a language and not simply a communication system, research using signed administration of tasks has increased, and clinicians have attempted to adapt or develop instruments for use with deaf clients. However, simply signing instructions or test stimuli does not “translate” a test into ASL even when the instructions or items are interpreted into linguistically accurate ASL. A number of challenges and issues arise when attempting to either modify an English-based measure for use with ASL or develop measures directly in ASL. These challenges and issues are reviewed as they relate to the broad areas of language assessment, the evaluation of mental status, memory testing, and the assessment of executive functioning, and the reader is directed to further materials that address each area in greater depth.