The twofold purpose of this meta-analysis was to determine the relative importance of decoding skills to reading comprehension in reading development and to identify which reader characteristics and reading assessment characteristics contribute to differences in the decoding and reading comprehension correlation. A meta-analysis of 110 studies found a sizeable average corrected correlation ([reading comprehension = 0.74]). Two reader characteristics (age and listening comprehension level) were significant moderators of the relationship. Several assessment characteristics were significant moderators, particularly for young readers: the way that decoding was measured and, with respect to the reading comprehension assessment, text genre; whether or not help was provided with decoding; and whether or not the texts were read aloud. Age and measure of decoding were the strongest moderators. We discuss the implications of these findings for assessment and the diagnosis of reading difficulties.