This short review describes our recent approaches and strategies for the development of quartz crystal microbalance (QCM)-based odor sensor systems for environmental and human health monitoring. QCM electrodes, which were modified with sensitive nanometer-thick coatings via layer-by-layer deposition, were used to develop a system for measuring significant environmental changes in indoor air. Identification of the origin of environmental changes was possible via differential signal analysis of the obtained data. The sensors showed different responses to humidity changes, hazardous gas (ammonia), or cigarette smoke exposure. In addition, QCM sensors with porous films comprising silica nanoparticles and poly(allylamine hydrochloride) (PAH) were fabricated via an electrostatic self-assembly method and they exhibited considerable sensitivity to relative humidity. The infusion of poly(acrylic acid) (PAA) into the multi-layer porous film enabled the construction of a highly sensitive and selective QCM sensor device for the detection of gaseous ammonia. Two types of QCM sensors, with and without PAA, enabled the simultaneous quantitative detection of humidity and ammonia. Preliminary tests were conducted to detect low concentrations of ammonia in human breath, which are of clinical relevance. The results obtained showed that the sensor can detect ammonia in human breath at pathological levels (greater than 3 ppm).