Even though research in the field of functional near-infrared spectroscopy (fNIRS) has been performed for more than 20 years, consensus on signal processing methods is still lacking. A significant knowledge gap exists between established researchers and those entering the field. One major issue regularly observed in publications from researchers new to the field is the failure to consider possible signal contamination by hemodynamic changes unrelated to neurovascular coupling (i.e., scalp blood flow and systemic blood flow). This might be due to the fact that these researchers use the signal processing methods provided by the manufacturers of their measurement device without an advanced understanding of the performed steps. The aim of the present study was to investigate how different signal processing approaches (including and excluding approaches that partially correct for the possible signal contamination) affect the results of a typical functional neuroimaging study performed with fNIRS. In particular, we evaluated one standard signal processing method provided by a commercial company and compared it to three customized approaches. We thereby investigated the influence of the chosen method on the statistical outcome of a clinical data set (task-evoked motor cortex activity). No short-channels were used in the present study and therefore two types of multi-channel corrections based on multiple long-channels were applied. The choice of the signal processing method had a considerable influence on the outcome of the study. While methods that ignored the contamination of the fNIRS signals by task-evoked physiological noise yielded several significant hemodynamic responses over the whole head, the statistical significance of these findings disappeared when accounting for part of the contamination using a multi-channel regression. We conclude that adopting signal processing methods that correct for physiological confounding effects might yield more realistic results in cases where multi-distance measurements are not possible. Furthermore, we recommend using manufacturers' standard signal processing methods only in case the user has an advanced understanding of every signal processing step performed.