Classical image processing methods often face great difficulties while dealing with images containing noise and distortions. Under such conditions, the use of soft computing approaches has been recently extended to address challenging real-world image processing problems. The automatic detection of Leukocytes or White Blood Cells (WBC) still remains as an unsolved issue in medical imaging. The analysis of WBC images has engaged researchers from fields of medicine and image processing alike. Since WBC can be approximated by an ellipsoid form, an ellipse detector algorithm may be successfully applied in order to recognize such elements. This chapter presents an algorithm for the automatic detection of leukocytes embedded into complicated and cluttered smear images that considers the complete process as a multi-ellipse detection problem. The approach, which is based on the Differential Evolution (DE) algorithm, transforms the detection task into an optimization problem whose individuals represent candidate ellipses. An objective function evaluates if such candidate ellipses are actually present in the edge map of the smear image. Guided by the values of such function, the set of encoded candidate ellipses (individuals) are evolved using the DE algorithm so that they can fit into the leukocytes which are enclosed within the edge map of the smear image. Experimental results from white blood cell images with a varying range of complexity are included to validate the efficiency of the proposed technique in terms of its accuracy and robustness.