We present an extensive review of genetic regulatory networks (GRNs) from a system biology perspective, and discuss pertinent research issues related to GRNs such as roles of feedback loops, and internal and external noise. A succinct review of mathematical modelling is also given as mathematical modelling is central to understand the complex molecular living systems. We discuss tryptophan production system in Escherichia coli bacteria, as an example, to illustrate how feedback loops originate, and finally we present a development of a mathematical model of circadian rhythms of Drosophila (fruit fly) as a comprehensive illustration of building a system model from components. We attempt to integrate experimentally acquired molecular biology knowledge in the model developments and discussions to emphasise the importance of being true to the data and insights in the experimental molecular biology. The experimental knowledge and insights should drive the efforts in development of mathematical and computational models of living systems, not the other way around, and this is a challenging task.