Mechanisms of photophysical, photobiological, and therapeutic action of light on blood in vivo are discussed based on results of spectral and clinical studies of blood, plasma, and erythrocytes. Spectral manifestations of photochemical reactions initiated in blood by therapeutic doses of radiation in vivo with light of different wavelengths are considered. Spectral and clinical results of blood investigations are compared for patients whose complex treatment included intravenous blood irradiation and magnetotherapy. Mechanisms for secondary (dark) reactions induced by the action of light on blood in vivo are discussed. The radiation of laser and non-laser light sources used at present for intravenous blood irradiation (365, 405, 450, 530, 632, 635, 808 nm) is shown to fall within hemoglobin absorption bands. The conclusion is made that blood absorption of laser and non-laser light radiation results in functional alteration of hemoglobin as a possible primary photoacceptor absorbing light radiation of the above wavelengths. The therapeutic effect of intravenous blood irradiation is initiated by hemoglobin functional activity modulation. Phototherapy is a means to correct it. Intravenous phototherapy should be considered as a therapeutic method that changes (provided that the dosage is correct) the balance of active oxygen species production and their inhibition by antioxidants.