Currently the ultimate success of anti-TB therapy is measured by the relapse rate within the first 2 years after treatment. The long duration of clinical trials that rely on this outcome constitute a disincentive for the pharmaceutical industry to develop new TB drugs. Biomarkers for relapse measurable during early treatment may shorten clinical trials. Additionally pre-treatment markers could allow stratification of patients into groups with different treatment requirements for improved clinical management. Currently there is a lack of sufficiently validated biomarkers with good individual predictive value and an urgent need for candidate markers and their evaluation in prospective studies. This review provides an overview of novel biomarkers for TB treatment response and outcome focusing on immunological markers in serum. Additionally, the challenges and roadblocks biomarker research is currently faced with are highlighted.