Limited information is available on alemtuzumab in the nonclinical trial setting. We evaluated its efficacy and safety in 42 consecutive unselected patients who received alemtuzumab monotherapy in British Columbia between October 2002 and August 2006. Information on patient demographics, baseline clinical characteristics, dose and schedule, clinical response, survival, and toxicities associated with alemtuzumab was collected retrospectively. Thirty-nine of 42 patients had chronic lymphocytic leukemia, two had mycosis fungoides, and one had T-cell post-transplant lymphoproliferative disorder. In contrast to previous reports, 42% were treated by community practitioners and 83% received alemtuzumab subcutaneously. The median time from diagnosis to alemtuzumab was 58 months. One of 42 patients (2%) achieved a complete response, 20 (48%) achieved a partial response, and 13 (31%) had stable disease. The post-alemtuzumab median overall survival was 15.1 months. Response to alemtuzumab correlated with an increased progression-free survival (11 vs. 3.6 months, p = 0.001) compared to that seen in non-responders. Significant adverse events included grade 3/4 neutropenia (76%), thrombocytopenia (45%), infections (60%) and death (12%). With careful monitoring, alemtuzumab can be safely administered in a wide variety of clinical settings, including community practice, and is associated with a high level of activity in situations with few available alternative treatment options.