This study is premised on the understanding that rising trends of urbanisation have led to increasing levels of interactionsbetween rural and urban settings and vice versa across the developing world. It is also envisioned that, rural-urban interactions play a significant role in supporting livelihoods especially of commuters. The overall objective of the study was to analyse the role of rural-urban interactions in supporting livelihoods of the commuters in Bugisu region. The study contributes to the understanding of livelihoods across spatial and sectoral boundaries looking at the synergistic coexistencefound between rural and urban and urban and rural settings. The study examined patterns of interaction and commuting activities in Bugisu region, looking at the influence of policy factors on commuting activities and commuter livelihoods strategies. The key concern was to establish a “fit” between rural-urban interaction and their potential for sustainable livelihoods. This study was conducted in Bugisu region, eastern Uganda covering the five districts of the then greater Mbale namely; Mbale, Manafa, Budduda and Sironko. The study employed both qualitative and quantitative methods of data collection and analysis.In examining patterns of interaction and commuting activities in Bugisu, the studynotes that rural Bugisu relates more closely with its urban centres. Mbale town, one of the oldest towns in the region serves as the hub of Bugisu region with, 69% of commuting activities in the area centred in it.