Monitoring of engineered systems consists of characterizing the normal behavior of the system and tracking departures from it. Techniques to monitor a system can be split into two classes based on their use of inputs and outputs of the system. Systems-based monitoring refers to the case when both inputs and outputs of a system are available and utilized. Conversely, symptomatic monitoring refers to the case when only outputs of the system are available. This thesis extended symptomatic and systems-based monitoring of biomedical systems via the use of non-stationary signal processing and advanced monitoring methods. Monitoring of various systems of the human body is encumbered by several key hurdles. First, current biomedical knowledge may not fully comprehend the extent of inputs and outputs of a particular system. In addition, regardless of current knowledge, inputs may not be accessible and outputs may be, at best, indirect measurements of the underlying biological process. Finally, even if inputs and outputs are measurable, their relationship may be highly nonlinear and convoluted. These hurdles require the use of advanced signal processing and monitoring approaches. Regardless of the pursuit of symptomatic or system-based monitoring, the aforementioned hurdles can be partially overcome by using non-stationary signal analysis to reveal the way frequency content of biomedical signals change over time. Furthermore, the use of advanced classification and monitoring methods facilitated reliable differentiation between various conditions of the monitored system based on the information from non-stationary signal analysis. The human brain was targeted for advancement of symptomatic monitoring, as it is a system responding to a plethora internal and external stimuli. The complexity of the brain makes it unfeasible to realize system-based monitoring to utilize all the relevant inputs and outputs for the brain. Further, measurement of brain activity (outputs), in the indirect form of electroencephalogram (EEG), remains a workhorse of brain disorder diagnosis. In this thesis, advanced signal processing and pattern recognition methods are employed to devise and study an epilepsy detection and localization algorithm that outperforms those reported in literature. This thesis also extended systems-based monitoring of human biomedical systems via advanced input-output modeling and sophisticated monitoring techniques based on the information from non-stationary signal analysis. Explorations of system-based monitoring in the NMS system were driven by the fact that joint velocities and torques can be seen NMS responses to electrical inputs provided by the central nervous system (CNS) and the electromyograph (EMG) provides an indirect measurement of CNS excitations delivered to the muscles. Thus, both inputs and outputs of this system are more or less available and one can approach its monitoring via the use of system-based approaches. / text