Title: Well-posedness of the Space-Time Fractional Diffusion Problems and Its Numerical Solutions The universality of anomalous diffusion phenomenon in physical and biological experiments has led to an intensive investigation on the fractional differential equations in recent years. The physical background includes modeling turbulent flow, chaotic dynamics charge transport in amorphous semiconductors, NMR diffusometry in disordered materials, and dynamics of a bead in polymer network, and so on. In this talk, we consider initial boundary value problems of the space-time fractional diffusion equation (STFDE) and its numerical solutions. STFDE is of interest not only in its own right, but also in that it constitutes the principal part in solving many other FPDEs. Two definitions, i.e. Riemann--Liouville definition and Caputo one, of the fractional derivative are considered in parallel. In both cases, we establish the well-posedness of the weak solution. Moveover, based on the proposed weak formulation, we construct an efficient spectral method for numerical approximations of the weak solution. The main results are as follows: First, a theoretical framework for the variational solution of the space-time fractional diffusion equation is developed. We find suitable functional spaces and norms in which the space-time fractional diffusion problem can be formulated into an elliptic weak problem, and the existence and uniqueness of the weak solution is then proved by using existing theory for elliptic problems. Secondly, we show that in the case of Riemann--Liouville definition, the well-posedness of the space-time fractional diffusion equation does not require any initial conditions. This contrasts with the case of Caputo definition, in which the initial condition has to be integrated into the weak formulation in order to establish the well-posedness. Finally, thanks to the weak formulation, we are able to construct some numerical methods for efficiently solving the space-time fractional diffusion problem.