As the release and amount of circulating biomarkers show considerable variations between individuals, single value determinations are often difficult to be interpreted on their diagnostic or prognostic significance on the individual level. However, changes of the biomarker levels in a specific person during the disease course are quite informative for the estimation of the efficacy of therapy or the early detection of recurrent disease because they consider only intraindividual variations. If methods for marker determination are maintained, preanalytical and analytical standard prerequistits are respected, thresholds for each marker have to be defined which exceeds the normal, intraindividual biological variation. Then continuous biomarker increases may be indicative for disease activity in terms of inefficient therapy response or tumor recurrence while decreasing values often are associated with activity reduction of cancer disease. Here, we review the current knowledge on biomarker kinetics in patients with non-small cell lung cancer (NSCLC) and discuss the conditions and pitfalls of their relevance for the estimation efficacy of therapy and the early detection of recurrent disease. Further, we suggest a scenario to reveal the power of the defined biomarker use in future and to include those markers into the individual management of NSCLC patients.