A retrospective chart review of 21 patients meeting core clinical criteria for behavioral or aphasic variants of frontotemporal lobar degeneration (FTLD) was conducted. Data recorded included Folstein Mini-Mental State Examination (MMSE) scores, medications prescribed, and subjective reports of behavioral symptoms from each visit. Behaviors were graded on a scale from 1 to 3 and totaled for each visit. Changes in MMSE and behavior scores between visits 1 month and 6 months apart where a new medication was started were analyzed using a paired t test and were compared between medication classes using an unpaired t test. Acetylcholinesterase inhibitors (AChEIs) were associated with a decrease in MMSE scores by 1.6 (P = .02) and an increase in total behavior scores by 1.0 (P = .03). Mean MMSE and behavior scores were statistically more improved by selective serotonin reuptake inhibitors than AChEIs (P = .04). This data suggest a potential worsening of objective measures of cognitive and behavioral symptoms in FTLD with AChEI treatment.