Cognitive deficits are related to impaired everyday functioning in multiple conditions and in healthy individuals. Treatment of cognitive functioning can be facilitated through either pharmacological or remediation strategies. The critical goals of cognitive enhancement are to improve everyday functioning in multiple domains. This chapter describes the strategies that are most desirable for the treatment of cognitive impairments and detection of potential benefits of treatment in cognitive and functional domains. These strategies include the use of performance-based assessments of cognition and functioning and the appropriate use of observational strategies to detect changes. Finally, we define several outcome-related goals and discuss the practicality of their measurement.