OBJECTIVES: SIMpill is a medication adherence management system using cellular networks to provide real-time information about, and support to, patients on long term medication. The SIMpill system is described in detail. METHODS: A pilot was carried out from July 1, 2006 to April 12, 2007 in Cape Town, South Africa.  Patients diagnosed with Tuberculosis were taken onto the pilot as they arrived at the clinics until the desired number of patients was achieved. Contrary to the standard DOTS protocol, patients were allowed to self medicate either at their homes or their places of work, supported by the SIMpill system. RESULTS: Of the 155 TB patients enrolled in the pilot study the following results were recorded: 12 patients (8%) did not have adequate documentation of outcomes at the end of the pilot and are excluded from the data. One patient (0.8%) was recorded as a sputum positive treatment failure. Seven patients (3.3%) interrupted their treatment whilst four patients transferred to other clinics or died during the pilot study.  A total of 131 patients (91.6% including unrelated interruptions, 94.2% excluding unrelated interruptions) were recorded as successful treatments.  This is contrasted with the background treatment success rate under the DOTS regimen of 76.4% at the same time in the same communities. CONCLUSIONS: It is concluded that the SIMpill system is practical to implement, could dramatically improve treatment success in TB patients and warrants further study, both in TB and other conditions.