Manufacturing systems are crucial for the Industry. The Toyota Central Research Laboratories have recently developed a number of highly successful simulation based methods to understand and predict the behavior of a manufacturing system. These methods include a reliable quantitative bottleneck detection, resulting in a machine sensitivity analysis including a prediction model of the effect of machine changes, and a blocking and starving analysis, resulting in a prediction model of the effects of buffers and a subsequent buffer optimization. The novel idea of these methods is a holistic view of the manufacturing system, i.e. understanding the system by analyzing the relations between the machines instead of analyzing machines independently. This paper provides the framework of the holistic manufacturing analysis and a brief summary of the methods already developed using this framework.