It has been argued recently that knowledge is the norm of practical reasoning. This norm can be formulated as a bi-conditional: it is appropriate to treat p as a reason for acting if and only if you know that p. Other proposals replace knowledge with warranted or justified belief. This paper gives counter-examples of both directions of any such bi-conditional. To the left-to-right direction: scientists can appropriately treat as reasons for action propositions of a theory they believe to be false but good approximations to the truth for present purposes. Cases based on a variant of Pascal’s Wager and actions performed by a skeptic also illustrate the point. To the right-to-left direction: in certain circumstances, it can be unreasonable for a scientist to reason from propositions of a theory she knows to be true.