Ordinary doping by electrons (holes) generally means that the Fermi level shifts towards the conduction band (valence band) and that the conductivity of free carriers increases.Recently, however, some peculiar doping characteristics were sporadically recorded in different materials without noting the mechanism: electron doping was observed to cause a portion of the lowest unoccupied band to merge into the valance band, leading to a decrease in conductivity. This behavior we dub as "anti-doping" was seen in rare-earth nickel oxides SmNiO3, cobalt oxides SrCoO2.5, Li-ion battery materials and even MgO with metal vacancies. We describe the physical origin of anti-doping as well as its inverse problemthe "design principles" that would enable intelligent search of materials. We find that electron anti-doping is expected in materials having pre-existing trapped holes and is caused by annihilation of such "hole polarons" via electron doping. This may offer an unconventional way of controlling conductivity.Doping of carriers into solids plays a crucial role both in controlling their physical properties (conductivity, superconductivity, metal-insulator transitions) via shifting of the Fermi level (EF), and ultimately enables transport-based device technologies (electronics, spintronics, optoelectronics) [1,2]. Successful doping of insulators or semiconductors by electrons (holes) means that EF shifts towards the conduction band (valence band) and that the conductivity of free electrons (free holes) increases. The relationship EF(n) between the carrier density n and the Fermi energy is textbook predictable [3] provided the density of states D(ε) of the host solid (and hence its electronic structure) remains rigid (unperturbed by the doping process itself).Recently, however, peculiar doping characteristics were noted in a number of disconnected cases, where electron doping was observed to significantly increase the band gap, and lead to a colossal decrease (several orders of magnitude) in conductivity. We will refer to such phenomenology as "anti-doping". Such observations were recorded in materials systems such as rare-earth nickel oxides SmNiO3 [4][5][6] and in ordered-vacancy cobalt oxides SrCoO2.5 [7]. In contrast to normal doping that is governed by classic defect physics [1,8], anti-doping represents perhaps the most unprecedent extreme form of a nonrigid response of D(ε) to doping, reversing entirely the expected trendreducing, rather than increasing conductivity by doping. In sharp contrast to the well-established "unsuccessful doping" that is usually detrimental to applications, anti-doping paves a new route for band gap modulation and resistance switching, and thus promises new directions of doping-induced multiple functionalities such as fuel cells, electric field sensors, Li-ion battery materials, and optical devices [4][5][6][7]9]. Because of the disparity in properties of the systems where such peculiar doping characteristic was observed, it would be tempting to dismiss these observations as specific idiosyncr...