The aim of this paper is to show the possible significance, and usefulness, of various non-self-adjoint operators for suitable Observables in nonrelativistic and relativistic quantum mechanics, and in quantum electrodynamics. More specifically, this work deals with: (i) the maximal Hermitian (but not self-adjoint) time operator in nonrelativistic quantum mechanics and in quantum electrodynamics; (ii) the problem of the four-position and four-momentum operators, each one with its Hermitian and anti-Hermitian parts, for relativistic spin-zero particles. Afterwards, other physically important applications of non-self-adjoint (and even non-Hermitian) operators are discussed: in particular, (iii) we reanalyze in detail the interesting possibility of associating quasi-Hermitian Hamiltonians with (decaying) unstable states in nuclear physics. Finally, we briefly mention the cases of quantum dissipation, as well as of the nuclear optical potential.