The intensive use of chemicals through decades has been selecting resistant popula‐ tions of several insect species to distinct classes of insecticides, like neurotoxics, in‐ sect growth regulators, and toxins derived from bacteria. Insecticide resistance is nowadays a huge challenge for control programs of pests of rural practices and principally to the management of arthropod vector-borne diseases. Several behavio‐ ral, physiological, and molecular mechanisms can be selected for avoiding toxic ef‐ fects of insecticides in the insect organism. These changes are genetic traits that arise randomly and spread throughout the population along time, under an envi‐ ronment with insecticide selective pressure. However, new rapidly achieved char‐ acteristics can present a fitness cost to their harbors, with negative effects in development and reproductive aspects. In this way, in the absence of insecticides, susceptible individuals may present reproductive advantages and then the popula‐ tion resistance levels would tend to decrease. If the selection pressure persists, how‐ ever, compensatory genes known as modifiers can be selected, ameliorating the negative effects caused by the resistance genes themselves or their pleiotropic ef‐ fects. In this chapter, we present a review of research articles that describe some fitness costs associated with insecticide resistance, trying to correlate with the known se‐ lected mechanisms whenever possible, under an evolutionary perspective. Exam‐ ples from natural population, as well as lineages artificially selected for resistance in the laboratory, were considered. Although new tools of vector control are currently being tested under field conditions, the use of insecticides will remain with an im‐ portant role in the near future at least. In this sense, the knowledge of evolutionary processes of insecticide resistance is crucial to try to revert the resistant status of natural populations and to avoid resistance to new compounds, maintaining this strategy as an effective alternative of insect control.