Here we build from the central strength of the existing definition of dyslexia—its emphasis on neurobiological origins—and proffer a set of seven core principles for a new, more comprehensive conceptualization of dyslexia. These principles derive from two major research directions: (1) the still evolving history of attempts to explain dyslexia, including in varied writing systems; and (2) the study of the reading brain circuit, its development, and its genetic and environmental influences. What emerges from connecting these two directions is a dynamic conceptualization of dyslexia that incorporates the extensive research on the heterogeneity of dyslexia and the interdependent contributions of multiple biological and socio-cultural risk and preventive factors. A new definition of dyslexia, therefore, needs to transcend both past unitary characterizations and past assumptions based largely on the English orthography. Such a conceptualization references the ways that different languages interact with the reading brain circuit to produce different sources of reading failure. Similarly, the characteristics and consequences of dyslexia that have been considered as secondary sequela (e.g., reduced reading comprehension, social-emotional issues) should be part of a more comprehensive narrative. Of critical importance, any definition of dyslexia should clarify persisting misconceptions that associate dyslexia with a lack of intelligence, potential to learn, or talents. Thus, the overall purpose of such a definition should serve as an instrument of knowledge and an enduring reason for pursuing growth in reading for the individual, the educator, and the public.