The influence of the primary molecular parameters chain configuration, architecture and molecular weight (MW) on the mode of mechanical breakdown is discussed for two series of (amorphous) thermoplastic polymers, methyl methacrylate glutarimide copolymers and amorphous semi-aromatic polyamides. Structural and dynamic analyses and fracture mechanical methods applied to such adequately chemically modified (glassy) polymers permit us to show and to explain the effect of intrinsic variables on local molecular motions and on the competition between chain scission, disentanglement and segmental slip, which in turn determine the dominant mode of instability and plastic behaviour. Above a critical molecular weight, toughness depends most strongly on the entanglement density; a positive effect of the intensity of sub-Tg relaxations and in-chain cooperative motions on the toughness of these materials is clearly evident.