A microfluidic device, or a Lab-on-a-Chip (LoC), performs lab operations on the microscale through the manipulation of fluids. The design and fabrication of such devices usually is a tedious process, and auxiliary tools, such as simulators, can alleviate the necessary effort for the design process. Simulations of fluids exist in various forms and can be categorized according to how well they represent the underlying physics, into so-called abstraction levels. In this work, we consider simulation approaches in 1D, which are based on analytical solutions of simplified problems, and approaches in 2D and 3D, for which we use two different Computational Fluid Dynamics (CFD) methods—namely, the Finite Volume Method (FVM) and the Lattice-Boltzmann Method (LBM). All these methods come with their pros and cons with respect to accuracy and required compute time, but unfortunately, most designers and researchers are not aware of the trade-off that can be made within the broad spectrum of available simulation approaches for microfluidics and end up choosing a simulation approach arbitrarily. We provide an overview of different simulation approaches as well as a case study of their performance to aid designers and researchers in their choice. To this end, we consider three representative use cases of pressure-driven and channel-based microfluidic devices (namely the non-Newtonian flow in a channel, the mixing of two fluids in a channel, and the behavior of droplets in channels). The considerations and evaluations raise the awareness and provide several insights for what simulation approaches can be utilized today when designing corresponding devices (and for what they cannot be utilized yet).