Given graphs $X$ and $Y$ with vertex sets $V(X)$ and $V(Y)$ of the same cardinality, we define a graph $\mathsf{FS}(X,Y)$ whose vertex set consists of all bijections $σ:V(X)\to V(Y)$, where two bijections $σ$ and $σ'$ are adjacent if they agree everywhere except for two adjacent vertices $a,b \in V(X)$ such that $σ(a)$ and $σ(b)$ are adjacent in $Y$. This setup, which has a natural interpretation in terms of friends and strangers walking on graphs, provides a common generalization of Cayley graphs of symmetric groups generated by transpositions, the famous $15$-puzzle, generalizations of the $15$-puzzle as studied by Wilson, and work of Stanley related to flag $h$-vectors. We derive several general results about the graphs $\mathsf{FS}(X,Y)$ before focusing our attention on some specific choices of $X$. When $X$ is a path graph, we show that the connected components of $\mathsf{FS}(X,Y)$ correspond to the acyclic orientations of the complement of $Y$. When $X$ is a cycle, we obtain a full description of the connected components of $\mathsf{FS}(X,Y)$ in terms of toric acyclic orientations of the complement of $Y$. We then derive various necessary and/or sufficient conditions on the graphs $X$ and $Y$ that guarantee the connectedness of $\mathsf{FS}(X,Y)$. Finally, we raise several promising further questions.