Three novel and two commercially available low-cost point-of-use (PoU) water treatment technologies were comparatively evaluated using a specialized comparison framework targeted at them. The comparison results and specialized framework have been discussed. The PoU systems were evaluated principally in terms of performance, flow rate and cost per volume of water treated (quantitatively), ease of use, potential acceptability and material availability (qualitatively) with main focus on rural and suburban settings. The three novel systems assessed were developed in an ongoing research project aimed at developing a multibarrier low-cost PoU water treatment system. The comparative evaluation and analysis revealed that the commercially available systems may often produce water free of pathogens (with an apparent 100% removal for E. coli and fecal coliforms) but may not be affordable for application to the poorest groups in much of the developing world. The novel systems, which were principally constructed from local materials, were more affordable, can supply relatively safe water and can be constructed by users with minimal training. Overall, bacterial removal effectiveness, ease of use, flow rate, material availability, cost and acceptability aspects of water were identified as key to potential adoption and sustainability of the evaluated low-cost PoU systems.