It is an error by the trier of law (judge), or the trier of fact (the jury, or the judge if it is a bench trial), or malfeasance by one of the trying attorneys, which results in an unfair trial.
It is to be distinguished from harmless errors which do not rise to a level which brings the validity of the judgment into question and thus do not lead to a reversal upon appeal.
The criteria for determining what constitutes a "substantial right" is somewhat vague, however, being that it varies from case to case, each presenting a slightly different interpretation of which rights are essential, or significant enough to warrant this sort of legal protection.
Failure of the judge to remedy it during the trial is reversible error.
In cases such as unfairly or illegally concealing evidence, there is no error on the part of the court but the court's decision may still be vacated and the matter returned for a new trial, because there is no other way for justice to be granted.