Inertial microfluidics has brought enormous changes in the conventional cell/particle detection process and now become the main trend of sample pretreatment with outstanding throughput, low cost, and simple control method. However, inertial microfluidics in a straight microchannel is not enough to provide high efficiency and satisfying performance for cell/particle separation. A contraction–expansion microchannel is a widely used and multifunctional channel pattern involving inertial microfluidics, secondary flow, and the vortex in the chamber. The strengthened inertial microfluidics can help us to focus particles with a shorter channel length and less processing time. Both the vortex in the chamber and the secondary flow in the main channel can trap the target particles or separate particles based on their sizes more precisely. The contraction–expansion microchannels are also capable of combining with a curved, spiral, or serpentine channel to further improve the separation performance. Some recent studies have focused on the viscoelastic fluid that utilizes both elastic forces and inertial forces to separate different size particles precisely with a relatively low flow rate for the vulnerable cells. This article comprehensively reviews various contraction–expansion microchannels with Newtonian and viscoelastic fluids for particle focusing, separation, and microfluid mixing and provides particle manipulation performance data analysis for the contraction–expansion microchannel design.